Pressure-dependent studies of the optical spectra of dissolved solutes have provided a wealth of information about solute-solvent interactions. In biophysical chemistry, pressure has lone been used as an environmental variable to probe the interactions of proteins with ligands, to study conformational equilibria and protein dynamics. The pressure dependence of protein unfolding has also been a subject of extensive study. Very recently, high resolution X-ray and NMR techniques have been used to obtain atomic resolution information concerning pressure effects on proteins. The overall objective of the proposed research is to further explore through computer simulations the effects of applied pressure on equilibrium and dynamic aspects of protein conformation, and in particular to probe the nature of the protein-solvent interface. In a preliminary study of pressure effects on Pancreatic Trypsin Inhibitor, a strikingly large compressibility of the protein hydration layer was observed. A framework will be developed to characterize more systematically the thermodynamic properties of the protein hydration layer. Studies of pressure effects on Pancreatic Trypsin Inhibitor will be extended to lysozyme and staphylococcal nuclease where high resolution data is available to comparison with the simulations. Simulations of smaller model systems will also be carried out to help clarify the relationship between the thermodynamic properties of the protein hydration layer and the underlying solute-solvent interactions.